In the process of tumor invasion, the connective tissue degrades by several lytic mechanisms. Increased collagenase activity has been found to be associated with certain neoplastic tissues. However due to the absence of any specific criteria for the detection of host or tumor enzyme, it has not been possible to demonstrate whether the increased neoplastic enzyme activity is due to the overproduction of tumor-enzyme or host enzyme. We intend to study both the host and the tumor enzyme in detail in order to find out if biologically they are two separate entities or if they are related on account of their common sharing of one or more components of the collagenase system. For this purpose, we plan to use a heterologous human tumor-nude mouse system in which the two different collagenolytic enzymes and their precursor components may be identified by their unique immunogenic properties. Mouse skin, normal tissue and human neoplasm will be cultured, the collagenase produced in the culture medium will be isolated and purified, and used as an antigen in rabbits. Cultured human tumor cells will be injected into nude mice, and the surrounding host tissue will be examined by immunohistologic techniques using tagged anticollagenase antibodies to study the distribution of the two enzymes. Further studies will explore the production of procollagenase and activators by both host and tumor tissue with the aim of examining interactions between the component parts of the two enzyme systems.